Adverse drug reactions reporting practice and associated factors among community health extension workers in public health facilities, Southwest, Nigeria

Introduction timely adverse drug reactions (ADRs) reporting has contributed immensely towards public health safety. Community health extension workers (CHEWs) provides basic medical care in rural areas. This study assessed the knowledge, attitude, practice, and determinants of ADRs reporting among CHEWs in public health institutions, Southwest, Nigeria. Methods a cross-sectional survey of 333 CHEWs randomly selected from public health facilities using self-administered questionnaires. The questionnaire sought information on the knowledge, attitude and practice of CHEWs towards ADRs reporting. The knowledge and attitude questions were scored and categorized. The association between dependent and independent variables assessed with bivariate and multivariate logistic regressions, and p < 0.05 considered statistically significant. Results among 333 respondents, 205 (61.6%) had encountered patients with ADRs but only 26 (12.6%) had reported it with yellow forms. About half, 169 (50.8%), and 191 (57.4%) respondents had a positive attitude and inadequate knowledge of ADRs reporting respectively. Sex (aOR: 2.84, 95% CI: 2.10-7.10; p < 0.0001), working in Ogbomoso area (aOR: 3.3, 95% CI: 1.34-8.21; p=0.01), and training (aOR: 2.01, 95% CI: 1.20-3.42; p = 0.01) were factors associated with adequate knowledge. The determinant of ADRs reporting was training (aOR: 3.63, 95% CI: 1.13-11.63; p = 0.03). Conclusion though CHEWs had a slightly positive attitude, they had inadequate knowledge and poor ADRs reporting. The determinant of inadequate ADRs reporting knowledge and under reporting was lack of training. There is an urgent need for educational intervention programmes towards improving knowledge and practices of ADRs reporting among CHEWs.


Introduction
Adverse Drug Reactions (ADRs) constitute an important cause of morbidity and mortality worldwide [1] and have been reported as the sixth leading cause of death in the U.S after heart disease, cancer, stroke, pulmonary disease, and accidents [2]. In addition to potentially causing illhealth, ADRs impose a heavy economic loss on nations [3,4]. Despite the burden of ADRs, many times it is either not recognised as the cause of the patient´s problem, or when recognised, it may not be reported by health professionals [5][6][7]. The most common method of reporting ADRs worldwide is spontaneous reporting, which is done through pharmacovigilance [8][9][10][11]. However, the major problem of spontaneous ADR reporting worldwide is under reporting [5], but it is probably worse in developing countries. Inappropriate use of drugs is common in Africa [12]. It is expected that the ADRs emanating from the continent would be high. Contrarily, ADR reports from Africa represent the least of the report to the VigiBase [13,14]. The decision on post-marketing withdrawal of medicines relies on the ADRs reported, and consequently, the continent continually has the least post-marketing withdrawal of unsafe medicines [15].
The Pharmacovigilance activities in Nigeria are coordinated by the National Pharmacovigilance Centre (NPC), at the National Agency for Food and Drug Administration and Control. All healthcare providers are to report any observed ADRS as part of their professional responsibility to NPC. NPC receive, collate and analyze submitted ADRs and transmit such to the WHO Uppsala Monitoring Centre [16,17]. Studies have shown that between 2.0 and 7.3% of Physicians practising in urban areas of Nigeria reported ADRs [18][19][20][21]. Similarly, low reporting rates have been reported among health care workers in urban areas in Nigeria. Also, there were inadequate knowledge and a negative to a moderately positive attitude of ADR reporting among health care professionals [22][23][24][25][26][27]. In Nigeria, the majority of health care professionals work in urban centres. The rural areas are devoid of health care workers and facilities. Most of the health facilities in the rural areas are manned by the Community Health Extension Workers (CHEWs). CHEWs provide support in the management of minor medical illnesses, antenatal care, routine and Participants: they were CHEWs randomly selected from public primary and secondary health facilities in Oyo State. The PHC coordinators (for LGs) and hospital heads (secondary /general hospitals) were requested to randomly select one CHEW per health facility, as part of health care workers for the Malaria Action Program for States (MAPS) training. MAPS was case management training for acute uncomplicated malaria in Oyo State sponsored by FHI 360 and took place in all five zones. All CHEWs who provided verbal informed consent were asked to complete a self-administered study questionnaire on the first day, and submit the questionnaire the same day before leaving the venue of the training. A trained research assistant was employed for the research. And together with the principal investigator (PI) were available to clarify any question during the completion of the questionnaire.
Data sources/measurement: the study selfadministered questionnaire included four sections and was adapted from previous studies [20,21,28]. Section A contains information on the sociodemographic characteristics of the participants, section B, knowledge of ADR reporting, section C, attitude of ADR reporting and section D, practices of ADR reporting and an open question on suggested ways of improving ADR reporting. Twenty questions were used to assess the knowledge of ADRs reporting. The knowledge questions were Yes/No with one mark allocated for one correct response giving a total score of 20 marks. The attitude questions comprising of 15 questions and using a 3-point Likert scale (agree, neutral and disagree) was used to measure the participants´ level of agreement with the survey questions. The reliability test (Cronbach alpha) on SPSS version 21 for the knowledge questions/scale and attitude questions/scale was 0.88 (0.86, 0.90) and 0.87 (0.84, 0.89) respectively. The normality plot test (Kolmogorov-Smirnov and Q-Q plot) of both the knowledge and attitude score were not normally distributed. For the knowledge score, a score of more than or equal to 12 was ranked as adequate knowledge while a score of less than 12 was ranked as inadequate knowledge. For the attitude, a score greater than or equal to 32 (median score) was considered a positive attitude while a score of less than 32 was ranked as a negative attitude.
Variables: dependent variables-overall knowledge and attitude of CHEWs about ADR reporting, and ADRs reporting with form. Independent variables-Age, sex, years of professional experience, marital status, attended training on ADRs reporting, level of practice, and geographical zones.
Study size: the sample size was calculated using the Leslie Kish formula, n = pqZ 2 /d 2 [29]. Assuming 50% of the respondents will have adequate knowledge of ADRs reporting, the critical value for α at p < 0.05 of 1.96, precision (d)=5%. After adjustments for the population (number of CHEWs in the state=1,121) and 10% non-response, a minimum sample size of 317 was obtained.
Statistical methods: data was analysed using IBM-SPSS version 22. The continuous variables like age, years of professional experience, knowledge, and attitude score were summarized with mean (± standard deviation), or median (range) if not normally distributed. The categorical variables like sex, marital status, level of practice, geographical zones, ever received training, reporting ADRs with ADR form, knowledge, and attitude (categorized) were summarised using frequency and proportion. Association between knowledge (adequate and inadequate knowledge), attitude (positive and negative), reporting ADRs with forms and selected independent variables were assessed with odds ratios and Chi-square. Statistically significant variables in the bivariate analyses were included in multivariate analyses. Multivariate analyses were performed with binary logistic regression. The level of statistical significance was set at < 0.05.
Ethical consideration: the study was approved by the University of Ibadan/University College Hospital ethical review committee (UI/EC/12/0418). Verbal informed consent was obtained from the participants.

Results
Participants: a total of 400-questionnaires were distributed to the CHEWs, of which 333 were completed and returned within the stipulated time, given a response rate of 83.3%. The majority of survey respondents were female (78.4%) and the mean age of the respondents was 43.5 (±8.3) years. The median (range) years of professional experience was 18 (1 to 40) years. One-third of the respondents have ever received training on ADRs reporting ( Table 1).
Knowledge of community health extension workers on ADRs reporting: the majority of the respondents 246 (73.9%) knew that ADRs constitute an important problem in the medical practice. Awareness of the existence of the National Pharmacovigilance Centre (NPC) in Nigeria was low, 156 (46.8%) and only 63 (18.9%) respondents knew the location is in Abuja. The knowledge of ADRs to the agents (drugs, vaccines and medical devices etc.) to be reported was generally inadequate among the respondents. The median (range) proportion of the respondents who knew the ADRs to the agents to be reported was 41 (31.5 to 49.2). More than 70% of the respondents knew that suspected ADRs, confirmed ADRs, serious reactions and the reactions to the newly introduced drugs in the market should be reported. The mean knowledge score of the respondents was 10.2 (±5.3) while the median (range) score was 10 (0 to 20). One hundred and forty-two (42.6%) and 191 (57.4%) respondents had adequate and inadequate knowledge of ADRs reporting respectively.
Factors associated with community health extension workers knowledge of ADRs reporting: males had more knowledge of ADRs reporting than females, COR: 4.5, 95% CI 2.30-8.01; p<0.0001). Respondents who have ever had training on ADRs reporting were 1.83 times more likely to have adequate knowledge of ADRs reporting than those who have not had training. Those who are in secondary health facilities were about 47 times more likely to have adequate knowledge than those in the primary health care facilities. The determinant of adequate knowledge of ADRs reporting were male gender, respondents from Ogbomoso zone and ever received training on ADRs reporting ( Table 2).
The attitude of community health extension workers on ADRs reporting: the majority had unfavourable attitudes to most of the questions tested except to those on the usefulness of ADRs reporting information, 205 (61.6%), reporting preventing respondents from publishing a case series of ADRs, 175 (52.6%) and professional obligation of ADRs reporting, 221 (66.4%). The mean attitude score was 32.1 (±7.4) while the median (range) was 32 (15 to 45). About half 169 (50.8) had a positive attitude to ADRs reporting.
Factors associated with community health extension Workers´ positive attitude on ADRs reporting: the factors that were significantly associated with positive attitudes towards ADRs reporting were male gender and working in Okeogun zone. The determinant of positive attitudes towards ADRs reporting was respondents from the Okeogun zone, aOR: 4.51, 95% CI 1.9-11.01; p=0.001 (Table 3).
Practices of community health extension workers regarding ADRs reporting: about two-third, 205 (61.6%) respondents have observed patients with ADRs, but only 26 (12.6%) of the respondents had reported with ADRs forms. When asked about which drugs were suspected or confirmed as the cause of the observed ADRs, 23 respondents identified chloroquine, 15 identified cotrimoxazole, 6 identified procaine penicillin, 5 identified ivermectin, and 2 identified multiple medications. One hundred and ninety-two respondents (57.7%) indicated that they always consider the possibility of ADRs before prescribing, dispensing or administration of drugs. Only about one-third of the respondents have ever received training on ADRs reporting (Table 4).
Factors influencing ADRs reporting by community health extension workers: males were 2.73 times more likely to report ADRs than females. Other factors that were significantly associated with reporting ADRs were age less than 40 years, less than or equal to 10 years of professional experience, and those who have had training on ADRs reporting. The only determinant of ADRs reporting was training, aOR: 3.63, 95% CI 1.13-11.63; p=0.01 (Table 5).

Discussion
The main method of preventing ADRs worldwide is through spontaneous reporting [10,11,30], the limiting factor of which is underreporting. Underreporting of ADRs is related to knowledge, attitude and practice of health workers towards ADRs reporting [20,28,31,32]. This study assessed the knowledge, attitude, practice and determinants of ADRs reporting by CHEWs in public health facilities. The respondents had a slightly positive attitude, inadequate knowledge and poor ADRs reporting. The determinant of ADRs reporting among the respondents was training. This study revealed inadequate knowledge of ADRs reporting by the respondents. Only one-third of the respondents have ever received training on ADRs reporting, and this may be an important contributory factor. Pharmacovigilance is not included in the curricula of many training schools in developing countries, and healthcare professionals only become aware during practice. Moreover, the majority of the respondents work in primary health care facilities where exposure to information on ADRs reporting are lacking. , as positively influencing ADRs reporting. However, our study found male respondents to be more likely to report ADRs than females. Males may have more aptitude to report ADRs than their females´ counterparts as against what was mostly reported by previous studies. Also, respondents aged less than 40 years and those with less than or equal to 10 years of professional experience were more likely to report ADRs. However, these factors were not sustained after multivariate analysis. The fact that studies used different cut-offs for years of professional working experiences may explain the dissimilar findings. Contrary to a study in Ethiopia [38], our study did not obtain the level of education of the respondents, rather they were treated as one professional cadre. The limitations of this study included the possibility of selection bias, reporting and recall biases among the respondents. There was a long delay in publishing these results. To the best of our knowledge, this is the first study on knowledge, attitude and practices of ADRs reporting among CHEWs. The importance cannot be overemphasized in developing countries considering the shortage of health care workers and the continuing need for new vaccines and hence adverse events following immunization (AEFI) and drugs (hence ADRs) in the midst of emerging and re-emerging infectious diseases, including COVID-19. This study provides baseline information for designing an educational intervention for improving ADRs and AEFIs reporting by CHEWs.

Conclusion
Community health extension workers (CHEWs) working in the public health facilities of Oyo State, Southwestern Nigeria had inadequate knowledge and poor ADRs reporting but a relatively favourable attitude. The determinants of adequate knowledge of ADRs reporting were male gender, working in Ogbomoso zone and training, while the determinant of positive attitude was working in Okeogun zone. Training was the determinant of ADRs reporting among CHEWs. There is an urgent need for educational intervention programmes aiming at increasing the knowledge and modifying the attitude and practices of CHEWs towards increasing ADRs reporting.  Table 1: sociodemographic characteristics of community health extension workers in public health facilities, South-West Nigeria Table 2: factors associated with the knowledge of community health extension workers on adverse drug reactions reporting, South-West, Nigeria Table 3: factors associated with positive attitude of community health extension workers on adverse drug reactions reporting, South-west Nigeria Table 4: adverse drug reactions reporting practices of the community health extension workers in public health facilities, South-west Nigeria